Mercury activates vascular endothelial cell phospholipase D through thiols and oxidative stress
| Autor: | Thomas Hagele, Bruce F. Kaufman, Periannan Kuppusamy, M. Lakshmi Kuppusamy, Ulysses J. Magalang, Anita Gregory, Clay B. Marsh, Narasimham L. Parinandi, Jessica N. Mazerik |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
chemistry.chemical_element
010501 environmental sciences Pulmonary Artery Toxicology medicine.disease_cause 030226 pharmacology & pharmacy 01 natural sciences Antioxidants 03 medical and health sciences Enzyme activator 0302 clinical medicine Thiocarbamates medicine Phospholipase D Animals Sulfhydryl Compounds Cells Cultured Edetic Acid 0105 earth and related environmental sciences Chelating Agents chemistry.chemical_classification Reactive oxygen species Thimerosal Endothelial Cells Lipid signaling Methylmercury Compounds Mercury (element) Acetylcysteine Endothelial stem cell Oxidative Stress Enzyme chemistry Biochemistry Mercuric Chloride lipids (amino acids peptides and proteins) Cattle Environmental Pollutants Reactive Oxygen Species Oxidative stress |
| Zdroj: | International journal of toxicology. 26(1) |
| ISSN: | 1091-5818 |
| Popis: | Currently, mercury has been identified as a risk factor of cardiovascular diseases among humans. Here, the authors tested the hypothesis that mercury modulates the activity of the endothelial lipid signaling enzyme, phospholipase D (PLD), which is an important player in the endothelial cell (EC) barrier functions. Monolayers of bovine pulmonary artery ECs (BPAECs) in culture, following labeling of membrane phospholipids with [32P]orthophosphate, were exposed to mercuric chloride (inorganic form), methylmercury chloride (environmental form), and thimerosal (pharmaceutical form), and the formation of phosphatidylbutanol as an index of PLD activity was determined by thin-layer chromatography and liquid scintillation counting. All three forms of mercury significantly activated PLD in BPAECs in a dose-dependent (0 to 50 μM) and time-dependent (0 to 60 min) fashion. Metal chelators significantly attenuated mercury-induced PLD activation, suggesting that cellular mercury-ligand interaction(s) is required for the enzyme activation and that chelators are suitable blockers for mercury-induced PLD activation. Sulfhydryl (thiol-protective) agents and antioxidants also significantly attenuated the mercury-induced PLD activation in BPAECs. Enhanced reactive oxygen species generation, as an index of oxidative stress, was observed in BPAECs treated with methylmercury that was attenuated by antioxidants. All the three different forms of mercury significantly induced the decrease of levels of total cellular thiols. For the first time, this study revealed that mercury induced the activation of PLD in the vascular ECs wherein cellular thiols and oxidative stress acted as signal mediators for the enzyme activation. The results underscore the importance of PLD signaling in mercury-induced endothelial dysfunctions ultimately leading to cardiovascular diseases. |
| Databáze: | OpenAIRE |
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